The control of bone resorption by local regulation of osteoclast proliferation and function is poorly understood. However, there is much evidence that mononuclear cells play some role in these processes during bone resorption that accompanies chronic inflammatory processes such as periodontal disease. A dense mononuclear cell infiltrate is characteristically present during alveolar bone loss and one type of mononuclear cell, the lymphocyte, when stimulated is able to release a substance, osteoclast-activating factor, which causes osteoclast proliferation and bone resorption in vitro. The role of mononuclear cells in bone resorption will be studied in a unique mutation, the ia rat, in which teeth do not erupt and bone resorption is greatly reduced because of reduced osteoclast function. Bone resorption and osteoclast function can be restored in these rats by a single injection of mononuclear cells from spleen or thymus of normal littermates. The role of mononuclear cells in the restoration of osteoclast function will be studied by autoradiographic determination of the fate of 3H-thymidine-labelled donor cells in ia hosts, the effect of mononuclear cells implanted into Millipore chambers on ia osteoclasts, the effects of normal mononuclear cells on the structure and function of ia osteoclasts in vivo and in vitro, fractionation of the mononuclear cell pool to determine which cell population(s) is responsible for restoring osteoclast function, and the effects of normal mononuclear cells on the structure, function and differentiation of another phagocytic cell type in ia rats, the macrophage. Finally, the effects of mononuclear cells and elevated bone resorption on tooth eruption will be examined in this mutation. This study will increase our understanding of the local control of bone resorption in tooth eruption and should provide a rational basis for blocking elevations of bone resorption and eliminating the irreversible bone loss accompanying chronic inflammations such as periodontal disease.